721MO - Phase I, two-part, multicenter first-in-human (FIH) study of TORL-1-23: A novel claudin 6 (CLDN6) targeting antibody drug conjugate (ADC) in patient with advanced solid tumors

Background

TORL-1-23 is an ADC targeting the oncofetal protein CLDN6. A member of the claudin family of tight junction proteins, CLDN6 expression is limited to early stages of development, with aberrant expression in many cancers, including ovarian, endometrial, and testicular cancers.

Methods

Part 1 (escalation) and part 2 (expansion) enrolled patients (pts) with advanced solid tumors. TORL-1-23 is administered as a 30-min IV infusion Q3W. Study objectives include evaluation of safety, tolerability, DLTs, RP2D, antitumor activity, and correlation of CLDN6 levels with response. Part 1: Pts received TORL-1-23 across 10 dose levels (0.2 to 4.0 mg/kg). Part 2: Pts with CLDN6-expressing cancers will be evaluated to confirm the RP2D in ovarian cancer, NSCLC, and other cancers using a CLDN6 IHC companion diagnostic.

Results

As of 29-Apr-2024, 68 pts have been enrolled. Part 1 enrolled 48 pts with ovarian (n=35), testicular (n=5), endometrial (n=7), and NSCLC (n=1) cancers. Part 2 enrolled 20 pts with ovarian (n=11), endometrial (n=4), NSCLC (n=4), and testicular (n=1) cancers at 2.4 mg/kg (n=12) and 3.0 mg/kg (n=8) with pegfilgrastim. Part 1: Median prior lines of therapy were 4 (1-9). Treatment-related adverse events (TRAE) occurred in 85% of pts. G1/2 TRAEs (>20%) included fatigue (42%), peripheral neuropathy (40%), alopecia (38%), nausea (31%), anemia (31%), WBC count decrease (23%), and arthralgia (23%). The most common (≥10%) G3+ TRAE was neutropenia (23%). Part 2: CLDN6+ ovarian cancer cohort was limited to platinum resistant disease, 1-3 prior lines. The safety profile for 2.4mg/kg and 3.0mg/kg was consistent with previous reports. Febrile neutropenia, ILD, and ocular toxicities were not observed. Pts with CLDN6+ ovarian cancer, ORR was 21% (3/14) at 0.2-2.0mg/kg; 67% (4/6) at 2.4mg/kg, and 50% (6/12) at 3.0 mg/kg. 26 pts remain on treatment with one ongoing >100 weeks.

Conclusions

TORL-1-23 is well tolerated with promising preliminary antitumor activity in heavily-pretreated pts with CLDN6-expressing ovarian, endometrial, and testicular cancers. Dose expansion is ongoing at doses of 2.4mg/kg and 3.0mg/kg in CLDN6+ NSCLC and ovarian cancer, and CLDN6-low expressing tumors.

Clinical trial identification

NCT05103683.

Editorial acknowledgement

Legal entity responsible for the study

TORL Biotherapeutics.

Funding

TORL Biotherapeutics.

Disclosure

G.E. Konecny: Financial Interests, Personal and Institutional, Advisory Role: TORL Bio. A.E. Wahner Hendrickson: Financial Interests, Personal and Institutional, Advisory Role: TORL Bio. B. Winterhoff: Financial Interests, Personal and Institutional, Advisory Role: TORL Bio. A.A. Adjei: Financial Interests, Institutional, Coordinating PI, funding for clinical trial: Vyriad; Non-Financial Interests, Advisory Role, uncompensated Advisory Board member: Merck AG, Cagent Pharmaceuticals; Non-Financial Interests, Advisory Role, uncompensated Chair of Advisors: Swiss Rockets; Non-Financial Interests, Principal Investigator, Clinical Trials: Kronos Bio; Non-Financial Interests, Principal Investigator, Climical Trials: BionTech, Bridge Bio; Other, Editor-in-Chief of Journal of Thoracic Oncology and JTO CRR: International Association for the Study of Lung Cancer. A. Kung, L. Miller: Financial Interests, Personal, Member: TORL Bio. M.F. Press: Financial Interests, Personal and Institutional, Advisory Role: TORL Bio. I. Qazi, N. Scholler, H. Dokainish, S. Letrent: Financial Interests, Personal, Stocks/Shares: TORL Bio. D. Slamon: Financial Interests, Personal and Institutional, Member of Board of Directors: TORL Bio.